Abstract
Decoction of Chinese herbal medicine (CHM) Fuzheng Kang-Ai (FZKA for short) has been applied as adjuvant treatment strategy in advanced lung cancer patients for decades. We previously showed that FZKA decoction inhibited proliferation of non-small cell lung cancer (NSCLC) cells through activation of AMP-activated protein kinase alpha (AMPKα) signaling pathway, followed by inducing insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and forkhead homeobox type O3a (FOXO3a) proteins, and enhanced the inhibition effect of gefitinib in lung cancer cell growth via inactivating PI3-K/Akt-mediated suppressing of cell surface-associated mucin-1 (MUC1) expression. In this study, we investigated the molecular mechanism by which FZKA decoction affected cell apoptosis in lung cancer cells. Our results show that FZKA induced apoptosis in lung cancer cells. Mechanistically, FZKA activated the caspase-3, PARP, and caspase-9 activities. Both antiapoptotic and proapoptotic proteins from Bcl-2 family were deregulated by FZKA exposure in lung cancer cells. In addition, FZKA reduced protein expressions of signal transducer and activator of transcription 3 (STAT3) and Jun activation domain-binding protein 1 (Jab1), while it concomitantly increased p21 protein. Moreover, the inhibitor of caspase-3 resisted the effect of FZKA on induction of apoptosis. Finally, exogenous overexpression of STAT3 overcame FZKA-inhibited protein expressions of Bcl-2 and myeloid cell leukemia-1 (Mcl-1) as well as Bax and blocked FZKA-induced activities of caspase-3 and caspase-9. Our results show that FZKA decoction promotes lung cancer cell apoptosis through STAT3/Bcl-2/caspase-3 signaling pathways. This study unveils potential novel molecular mechanism by which FZKA controls growth of human lung cancer cells.
Highlights
Lung cancer is a leading cause of cancer-related death in the world [1]
Our results showed that highperformance liquid chromatography (HPLC) chromatograms in four drinks of Fuzheng Kang-Ai (FZKA) decoction have similar patterns, revealing that the FZKA decoction has a good stability (Figure 1)
We explored the potential mechanism by which FZKA affected apoptosis in non-small cell lung cancer (NSCLC) cells
Summary
Lung cancer is a leading cause of cancer-related death in the world [1]. In China, lung cancer is the most frequently diagnosed cancer in males (22.14%) and is the leading cause of cancer death in both males (27.21%) and females (21.91%) [2]. Despite major advances in combination treatments, the prognosis of non-small cell lung cancer (NSCLC) is still dismal and the 5-year survival rate with all stages and subtypes combined remains as low as 11% [3]. The Chinese herbal medicine (CHM) provides promising strategy for patients with late stage of lung cancer. Yangfei Kongliu Formula (YKF) combined with cisplatin significantly inhibited the growth and metastasis of lung cancer cells via TGF-β1 pathway [6]. Homeopathic Psorinum-6x triggered apoptosis in lung cancer A549 cells
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